The work proposed in this grant application involves an investigation by ultracentrifugal studies, intrinsic viscosity measurements, and other appropriate physicochemical methods of the extent to which substitution of different amino acid residues into chain positions involving alpha 1 beta 2 contacts and into positions other than those directly involved in the alpha 1 beta 2 contacts can influence tetramer-dimer equilibria in various hemoglobin types, and a study of the effect of substitutions involving alpha 1 beta 1 contacts upon monomer formation and denaturation. This would be accomplished by comparative studies upon human and animal hemoglobins, the structural differences of which are known. Another phase of the work involves the use of differential sedimentation techniques to study conformational differences between oxy and deoxy human sickle cell hemoglobin, and also between sickling and nonsickling deer hemoglobins. The purpose of such information is to add to the knowledge of the forces responsible for maintaining the compact three dimensional structure of hemoglobin and its variants, and to better understand how a single amino acid substitution, or deletion, in a critical position of the hemoglobin molecule may so disrupt the molecule that its normal function is destroyed and serious hematologic conditions are encountered.